Comparative Safety Analysis of Surgical Smoke From Transurethral Resection of the Bladder Tumors and Transurethral Resection of the Prostate

Comparative Safety Analysis of Surgical Smoke From Transurethral Resection of the Bladder Tumors and Transurethral Resection of the Prostate

Basic and Translational Science Comparative Safety Analysis of Surgical Smoke From Transurethral Resection of the Bladder Tumors and Transurethral Res...

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Basic and Translational Science Comparative Safety Analysis of Surgical Smoke From Transurethral Resection of the Bladder Tumors and Transurethral Resection of the Prostate Chen Zhao, Myung Ki Kim, Hyung Jin Kim, Sang Kyi Lee, Youn Jo Chung, and Jong Kwan Park OBJECTIVE METHODS

RESULTS

CONCLUSION

To analyze the gas generated from the transurethral resection of the prostate (TURP) and transurethral resection of bladder (TURB) tumor. Thirty-six smoke samples were collected from a continuous irrigation suction system during the TURP and the TURB. Then, they were subdivided into 2 groups: the group I (n ¼ 18; gases generated from the TURP) and the group II (n ¼ 18; gases generated from the TURB). We performed qualitative and quantitative analysis of the samples on gas chromatography/mass spectrometry. A more diverse type of gas was generated from the TURB as compared with the TURP. A further quantitative analysis was performed for 7 of 16 gases and 13 of 39 gases in the group I and group II, respectively. This showed that there was no significant difference in the concentration of propylene (propylene: 148.36  207.72 ug/g vs 96.956  135.138 ug/g) and 1-pentene (5137.08  2935.48 ug/g vs 4478.259  5787.351 ug/g) between the TURP and the TURB (P >.05). Our results showed that 39 and 16 types of gases were generated from the TURB and the TURP, respectively. There were differences in the types of gases between benign hypertrophic prostate and malignant bladder tumor tissues. This indicates that electrosurgery of malignant tissue is possibly more hazardous to those who are involved in the surgical operation. UROLOGY 82: 744.e9e744.e14, 2013.  2013 Elsevier Inc.

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urgical smoke has become an integral component of the atmosphere in the operating room since the electrocoagulation was first applied by Harvey Cushing in 1926.1 With the use of energy-based technologies, surgical smoke is generated when target cells are heated to the boiling point. This causes the membrane rupture and then scatters cellular contents into the irrigation solution, organ spaces, and the environment of operation room.2 The surgical smoke is commonly Financial Disclosure: The authors declare that they have no relevant financial interests. Funding Support: This study was supported by grant from Clinical Trial Center of Chonbuk National University Hospital (2012) granted from Ministry of Health and Welfare, Republic of Korea (A091220). From the Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, China; the Department of Urology, Medical School, and Institute for Clinical Medicine, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, South Korea; the Department of Anesthesiology, Medical School, and Institute for Clinical Medicine, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, South Korea; and the Center for University-wide Research Facilities, Chonbuk National University, South Korea Reprint requests: Jong Kwan Park, M.D., Department of Urology, Medical School, Chonbuk National University, Jeonju, South Korea. E-mail: [email protected] Submitted: November 21, 2012, accepted (with revisions): May 28, 2013

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ª 2013 Elsevier Inc. All Rights Reserved

composed of chemicals, blood and tissue particles, viruses and bacteria. Exposure to aerosols is considered harmful to the health of operating room personnels because it contains the cellular particles, deoxyribonucleic acid (DNA) constituents, toxic gases, mutagens, and carcinogens.3 The chemical compositions and aerodynamic sizes of particles vary significantly, depending on the type of procedure, personal technique, pathology of target tissue, type of energy imparted, power levels used, and the scope of surgery (cutting, coagulation, or ablation).4 An electrosurgery creates the particles whose size is <0.1 mm and a laser tissue ablation does larger particles (<0.3 mm). But the largest particles are generated using an ultrasonic scalpel (0.35-6.5 mm). These particles travel up to 100 cm from their point of production.2 Short-term exposure to aerosols has been shown to cause eye irritation, nausea, vomiting, headache, sneezing, weakness, and lightheadedness, whereas long-term exposure causes cancer in animals and it is also linked to higher incidence of cancer in humans.5 An electrosurgery is one of the most commonly used energy systems in transurethral prostate and bladder 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.05.028

surgery. During transurethral surgery, surgical smoke is generated when the target tissue is resected and vaporized. It has previously been shown that major chemical constituents include propylene, allene, isobutylene, 1,3-butadiene, vinyl acetylene, mecaptomethane, ethyl acetylene, diacetylene, 1-pentene, EtOH, piperylene, propenylacetylene, 1,4-pentadiene, cyclopentadiene, acrylonitrile, and butyrolactone in the gas generated from the transurethtral resection of prostate (TURP). Of these, 3 constituents (1,3-butadiene, vinyl acetylene, and acrylonitrile) are known to be extremely toxic and carcinogenic.6 The irrigation solution contains 2.7% sorbitol and 0.54% mannitol (Ursol irrigation; CJ, Seoul, South Korea), and generates a lesser diverse type of gas at lower concentrations as compared with normal saline.6,7 It has been speculated that malignant tissue produces more toxic gases because of its nature and pathophysiology. To date, however, few studies have examined the chemical composition of surgical smoke generated from the TURP or the transurethral resection of the bladder (TURB), which is the most effective surgical procedure in patients with bladder tumor. Given the above background, we conducted this study to analyze the gas generated from the TURP and the TURB.

MATERIALS AND METHODS Patients and Samples In the present study, we analyzed gases produced during TURP and TURB for the treatment of benign prostate hyperplasia and bladder tumor, respectively. Thus, we divided our patients into 2 groups: the TURP group and the TURB group. Patients with benign prostate hyperplasia underwent TURP and these patients also had lower urinary tract symptoms of mild severity or greater. In these patients, the prostate volume was >40 mL and the maximal flow rate was <15 mL/second. Patients with noninvasive bladder tumor, diagnosed on cystoscopy and biopsy, underwent TURB. Samples were divided into 2 groups: the group I (n ¼ 18; gases generated from the TURP) and the group II (n ¼ 18; gases generated from the TURB). The study was approved by the Institutional Review Board of our medical institution. All the patients submitted a written informed consent. The patients underwent TURP or TURB using warm irrigation solution to continuously maintain the temperature of the ventral penile skin at approximately 36 C. Operations were performed under spinal or general anesthesia. All the procedures were performed in the same operation theater with a positive pressure ventilation system.

Tuttlingen, Germany). Intraoperatively, we frequently applied surgical jelly to the meatus, thus attempting to prevent the injuries to urethral and meatal mucosa. An electrosurgical generator (AUTOCON; Karl Storz GmbH & Co.) was used for the simultaneous cutting and vaporization at a voltage of 150 W and coagulation at a voltage of 60 W.

Gas Sampling The gas was developed during TURP and TURB and collected from the upper portion of the bladder. Then, the mixture of the irrigation solution and the gas was aspirated through the tubing into a large vacuum pump bottle. The gas above the fluid was released from the bottle through a tube to an absorber (Tenax GR, Japan Analytic Industry, Tokyo, Japan). Its flow rate was maintained at 0.05 L/minute by a gas pump (mini pump P MP- 30, Shibata, Tokyo, Japan).

Analysis of Samples With the use of automated purge and trap sampler (JTD-505III, Japan Analytic Industry), we prepared gas samples for the gas chromatography/mass spectrometry (GC/MS) (QP2010 Plus, Shimadzu, Kyoto, Japan) and quantitative analysis.

Conditions of Purge and Trap The conditions of purge and trap were as follows: desorption temperature, 280 C; desorption time, 30 minutes; desorption gas flow rate, 50 mL/minute; cold trap for sample trapping, 40 C; cold trap for pyrolysis, 280 C; transfer line temperature, 280 C; needle heater, 280 C; cold trap heater, 200 C; head press, 86 MPa; column flow, 1.0 mL/minute; and split ratio, 1:100.

Conditions of GC/MS We performed the GC/MS (QP2010 Plus, Shimadzu) to analyze gas composition under the following conditions: DB-624 column (30 m  0.251 mm  1.40 mm, Agilent Technologies, Wilmington, DE); 30-600 mass scan; 0-30 minutes, oven temperature program (40 C for 3-minute hold, 10 C/ minute 260 C, 5-minute hold); ion source, 200 C; transfer line, 250 C; and electron multiplier voltage, 70 eV.

Statistical Analysis We analyzed the number and concentration of gases generated from the TURB and TURP. All the data were expressed as mean  standard deviation, for which we performed 1-way analysis of variance and Bonferroni’s multiple comparison tests. A P-value of <.05 was considered statistically significant. Statistical analysis was done using the SPSS Version 13.0 for Windows (SPSS, Chicago, IL).

RESULTS Preparation of the Irrigation Solution

The irrigation solution was prepared using a heater set at 40 C, which was slightly lower than the temperature set just before entering the sheath of the resectoscope. Urosol was used to irrigate the surgical sites and to prevent the occurrence of hemolysis during TURP and TURB.

Operative Procedure A transurethral surgery was performed using a 22-F continuousflow resectoscope and a cutting loop (Karl Storz GmbH & Co., UROLOGY 82 (3), 2013

Patient Characteristics In the TURP group, the mean age was 69.1  6.5 years and the mean volume of the prostate and transitional zone were 45.5  21.8 mL and 24.1  13.7 mL, respectively. But the mean prostate-specific antigen level was 3.1  2.6 ng/mL. The mean International Prostate Symptom Score and maximal flow rate were 21.7  8.2 and 12.7  7.6 mL/second, respectively. In addition, the mean resected prostate volume was 19.2  13.1 mL. 744.e10

Table 1. Qualification data of gas collected during transurethral surgery S No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

Group I Propylene Allene Isobutylene 1,3-Butadiene Vinyl acetylene Mercaptomethane Ethyl acetylene Diacethylene 1-Pentene Ethanol Piperylene Propenylacetylene 1,4-Pentadiene Cyclopentadiene Acrylonitrile Butyrolactone

Group II F, CNC, NS F, NS F, NS F, CH, CA, NS F, CH, NS NS CH, NS NA F, NS F, CA, NS F, NS NA F, NS F, NS F, CH, NS S, CNC, NS

Propylene 1-Chloro-1,1-difluoroethane Pentafluoroethane Acetaldehyde 1-Pentene Perfluorocaprylic aldehyde Ethanol Propanone(acetone) Isopropyl alcohol 2-Methoxyethanol Hexane Cyclohexane Benzene Isopentanal Heptene n-Heptane Toluene n-Octane 3-Methyloctane Ethylbenzene o-Dimethylbenzene (o-Xylene) m-Dimethylbenzene 2,6-Dimethyloctane Methylcyclohexane 2-Methylnonane 3-Methylnonane m-Ethyltoluene 1,3,5-Trimethylbenzene 3,3-Dimethyloctane Isopropylbenzene Ethylcyclohexane 5,6-dimethyl-Undecane 2,3-Dimethylnonane 2 Ethyl hexanol Dodecane 1,1-Ethylenedioxy-2-Phenylpropane 2,4-dimethyl-1-Decene Hexadecane Heptadecane

F, CNC, NS F, NS F, CA, CH, NS CA, CH, NS F, NS F, NS F, CA, NS F, CNS, NS F, CNS, NS F, NS F, CA, NS F, NS F, CA, CH, NS F, NS F, NS F, CNC, NS F, CH, NS F, NS F, NS F, CH, NS F, CH, NS F, CNC, NS F, NS F, NS F, NS F, NS F, NS F, NS NS F, NS F, NS NA NA NS F, NS NA NA F, NS F, NS

CA, carcinogenic to animals; CH, carcinogenic to humans; CNC, product contains a component that is not classifiable with regard to carcinogenicity based on International Agency For Research On Cancer (IARC) criteria; F, flammable; GROUP I, gases produced during transurethral resection of the prostate; GROUP II, gases produced during transurethral resection of bladder; NA, no available data; NS, harmful, but not flammable, and nonspecific to carcinogens; S, stable.

In the TURB group, the mean age was 70  11.6 years and the mean resected bladder tumor volume was 11.7  13.99 mL. Qualitative Analysis of the Samples With reference to the compounds registered in the National Institute of Standards and Technology database, we positively identified 16 compounds from the group I and 39 compounds from the group II (Table 1). Human carcinogens include 1,3-butadiene, vinyl acetylene, ethyl acetylene, and acrylonitrile in the group I and pentafluoroethane, acetaldehyde, benzene, toluene, ethylbenzene, and o-xylene in the group II. Moreover, animal carcinogens include 1,3-butadiene and ethanol in the group I and pentafluoroethane, acetaldehyde, ethanol, hexane, and benzene in the group II. Furthermore, gases with carcinogenic potential, yet to be classified as carcinogens by the International Agency for 744.e11

Research on Cancer, include propylene and butyrolactone in the group I and propylene, acetone, isopropyl alcohol, n-heptane, and m-dimethylbenzene (o-xylene) in the group II. Quantitative Analysis of the Samples Of the 39 constituents, propylene, pentafluoroethane, 1pentene, acetone, isopropyl alcohol, n-hexane, cyclohexane, benzene, toluene, o-xylene, m-ethyltoluene, 1,3,5-trimethyl benzene, and isopropyl benzene were subjected to quantitative analysis (Table 2). The remaining constituents could not be subjected to quantitative analysis because of a small number of samples (Fig. 1, Table 2). A more diverse type of gas was generated from the TURB as compared with the TURP (Fig. 1, Table 1). A further quantitative analysis was performed for 7 of 16 gases in the group I (Table 2).7 This showed that there UROLOGY 82 (3), 2013

Table 2. Quantification of chemical components in gas produced during resection of 1 g tissue

Retention Time 1 2 3 4 5 6 7 8 9 10 11 12 13

5.30 6.48 2.27 2.52 3.48 3.58 2.11

Group I Chemical Components

Group II Amount (ug/g)

Acrylonitrile 332.4  314.47 1,3-Butadiene 126.59  232.58 Ethyl acetylene 23.54  31.84 Isobutylene 35,869.31  18,920.96 1,4-Pentadiene 15.44  11.76 1-Pentene 5137.08  2935.48 Propylene 148.36  207.72

Retention Time 2.11 2.62 3.58 4.45 4.62 5.81 7.49 7.98 10.67 13.08 15.00 15.45 15.74

Chemical Components

Amount (ug/g)

Propylene 96.956  135.138 Pentafluoroethane 5.599  6.966 1-Pentene 4478.259  5787.351 Acetone 0.187  0.199 Isopropyl alcohol 4.949  5.581 n-Hexane 0.026  0.030 Cyclohexane 0.170  0.253 Benzene 0.210  0.224 Toluene 0.119  0.133 o-Xylene 0.080  0.079 m-Ethyltoluene 0.006  0.007 1,3,5-Trimethyl benzene 0.009  0.009 Isopropyl benzene 0.026  0.026

GROUP I, gases produced during transurethral resection of the prostate; GROUP II, gases produced during transurethral resection of bladder. Each value represents mean  standard deviation.

The amount of chemical components (ug/g)

10000.0 8000.0 6000.0 4000.0 2000.0 0.5 0.4 0.3 0.2 0.1 0.0

l ne ne ne ne ne ne ne ne ne zene ne ne ho yle etha ente ceto alco exa exa nze olue Xyle olue nze n op T -H cloh Be A pyl o- hylt be yl be Pr luoro 1-P n l f Et thy rop Cy pro m- ime p nta so o I e Is P Tr ,51,3

Figure 1. Chemical constituents of the gas generated from the transurethral resection of the prostate and the transurethral resection of bladder.

was no significant difference in the concentration of propylene (propylene: 148.36  207.72 ug/g vs 96.956  135.138 ug/g) and 1-pentene (5137.08  2935.48 ug/g vs 4478.259  5787.351 ug/g) between the TURP and the TURB (P >.05).

COMMENTS Our results showed that various types of gases are generated during electrosurgery. Of these, human carcinogens include 1,3-butadiene, vinyl acetylene, ethyl acetylene, and acrylonitrile in the group I and pentafluoroethane, acetaldehyde, benzene, toluene, ethylbenzene, and oxylene in the group II. Extremely flammable gases were generated in the group I (8 of 16) and in the group II (31 of 39). Their carcinogenic potential is currently evaluated. A more diverse type of toxic gases was generated at higher levels from the TURB as compared with the UROLOGY 82 (3), 2013

TURP. It is well known that surgical smoke has cytotoxic, genotoxic, and mutagenic effects on both patients and operating room personnels.8 The toxicity of acrylonitrile is based on the formation of cyanide. It releases hydrogen cyanide in the presence of water. Its short-term exposure would cause eye irritation, nausea, vomiting, headache, sneezing, weakness, and light-headedness. It has also been reported that its longterm exposure raises the incidence of cancer. Moreover, it has also been documented that its repeated or prolonged exposure to skin may irritate the skin and trigger the occurrence of dermatitis.9 Hydrogen cyanide is a more toxic substance. Once absorbed through the skin and lung, it may cause headache, weakness, throat irritation, vomiting, dyspnea, lacrimation, colic, and nervousness.10 Moreover, benzene irritates the eyes, nose, and respiratory tract and can also cause headache, dizziness, and nausea. Its long-term exposure even at low concentrations may cause blood diseases such as anemia and leukemia.11 In the present study, we attempted to detect gases released during electrosurgery within a range of the molecular weight (MW) of 40-500 on GC/MS. But we did not include carbon monoxide (CO, 28 MW) and carbon dioxide (CO2, 44 MW) although they may be generated from the TURP and the TURB. CO is of particular concern because it is immediately absorbed from the peritoneum into the bloodstream, creating a route for systemic intoxication, during laparoscopic procedure. CO binds to hemoglobin, thus forming carboxyhemoglobin and methemoglobin. This produces a hypoxic stress because of reduced oxygen-carrying capacity of the blood in healthy individuals. Therefore, hypoxic stress can further impair cardiovascular function in patients with cardiovascular diseases.12 Once ablated, the tissue 1 g may have a mutagenic effect whose intensity is equivalent to that of 3-6 cigarettes during laser-assisted and electrocautery, respectively.13 It has been earlier demonstrated that electrosurgical smoke produces a helium environment 744.e12

that reduces the clonogenicity of MCF-7 human breast carcinoma cells in a dose-dependent manner.14 Another study showed that Salmonella TA98 strain undergoes alterations in histidine metabolism once it is exposed to smoke extract from human tissue ablation.15 It remains unclear whether surgical smoke would also have a mutagenic effect on humans. But this deserves further studies, as suggested by cytogenetic data. Our results showed that 39 and 16 types of gases were generated from the TURB and the TURP, respectively.6 There were differences in the types of gases between benign prostatic and malignant bladder tumor tissues. This indicates that electrosurgery of malignant tissue is possibly more hazardous to those who are involved in the surgical operation. Moreover, it is also noteworthy that surgical smoke contains the viable malignant tumor cells, which can be transmitted to others. To date, no studies have reported that the malignant tumor cells have been transmitted to humans. It is highly possible that aerosolization of malignant cells is a potential threat to both operating room personnels and patients, the operator in particular, who is the most closely exposed to the source of surgical smoke during transurethral surgery. Over the years, medical professionals have been more aware of the hazardousness of viral exposure after the initial identification of human immunodeficiency virus and human papillomavirus from the surgical smoke. This suggests that it would potentially cause viral infections. On tissue culture using a CO2 laser equipment, the proviral human immunodeficiency virus DNA was retrieved from a suction tube that is routinely used to remove the plume.16 Another study reported that bovine papillomavirus DNA was detected from the laser aerosol,17 indicating that there is a possibility that other harmful viruses might also be present in surgical smoke. The American Occupational Safety and Health Administration estimates that more than 500,000 workers are exposed to laser and electrosurgical smoke each year, including surgeons, nurses, anesthesiologists, and operating room personnels.18 The surgical mask only captures large particles (>5 mm), but does not provide adequate protection in filtering smoke.19 It has been reported that the incidence of nasopharyngeal lesions because of a CO2 laser equipment was relatively higher in surgeons as compared with normal controls. This suggests that surgeons are at increased risks of developing nasopharyngeal lesions with the inhalation of laser plumes.20 In the present study, there was also a variability in the type of tissue because of the difference in smoke composition between the group I and group II. The limitations of the present study are that we sampled the different types of tissue, that is, the prostate tissue and the bladder, between the group I and group II. Further cadaver experiments are therefore warranted to identify the type of gases generated during the electrosurgery of

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nonmalignant tissue. In Korea, however, it is not easy to conduct a cadaver study not only because it poses an ethical problem but also both surgeries are done using a urosol solution. In addition, we failed to use the standardized technique of smoke collection. Furthermore, the operation room set-up was far from a controlled laboratory environment. These potential pitfalls may have skewed the results. In the quantitative evaluation by GC/MS, some gases (CO, CO2, O2, and N2) automatically enter the GC/ MS. In addition, we failed to quantify other chemical gases when we should measure the concentration of such gases as CO, CO2, O2, and N2, for which we needed to set a higher baseline owing to their higher levels. Further studies based on other methods are therefore warranted to clarify the amount of the gases and the safety limits for air concentration of each harmful composition.

CONCLUSION To prevent the inhalation of surgical smoke, a continuous irrigation and suction system during transurethral surgery is needed because surgical masks do not completely prevent smoke intake. Furthermore, a surgical smoke evacuation system or smoke filters, or both, should be developed and then made readily available to both operating room personnels and patients to ensure their safety during transurethral surgery. References 1. Cushing H. Electrosurgery as an aid to the removal of intracranial tumors. Surg Gynecol Obstet. 1928;47:751-784. 2. Alp E, Bijl D, Bleichrodt RP, et al. Surgical smoke and infection control. J Hosp Infect. 2006;62:1-5. 3. Barrett WL, Garber SM. Surgical smoke-a review of the literature: is this just a lot of hot air? Surg Endosc. 2003;17:979-987. 4. Weld KJ, Dryer S, Ames CD, et al. Analysis of surgical smoke produced by various energy-based instruments and effect on laparoscopic visibility. J Endourol. 2007;21:347-351. 5. Watson DS. Surgical smoke evacuation during laparoscopic surgery. AORN J. 2010;92:347-350. 6. Chung YJ, Lee SK, Han SH, et al. Harmful gases including carcinogens produced during transurethral resection of the prostate and vaporization. Int J Urol. 2010;17:944-949. 7. Park SC, Lee SK, Han SH, et al. Comparison of harmful gases produced during green light high performance system laser prostatectomy and transurethral resection of the prostate. Urology. 2012; 79:1118-1124. 8. Wu MP, Ernest YT. Complications and recommended practices for electrosurgery in laparoscopy. Am J Surg. 2000;179:67-73. 9. Wu JS, Monk T, Luttmann DR, et al. Production and systemic absorption of toxic byproducts of tissue combustion during laparoscopic cholecystectomy. J Gastrointest Surg. 1998;2:399-405. 10. Taravella MJ, Viega J, Luiszer F, et al. Respirable particles in the excimer laser plume. J Cataract Refract Surg. 2001;27:604-607. 11. Nezhat C, Winer WK, Nezhat F, et al. Smoke from laser surgery: is there a health hazard? Lasers Surg Med. 1987;7:376-382. 12. Walker NP, Mathews J, Newsome SW. Possible hazards from irradiation with the carbon dioxide laser. Lasers Surg Med. 1986;6: 84-86.

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13. Gatti JE, Bryant CJ, Noone RB, et al. The mutagenicity of electrocautery smoke. Plast Reconstr Surg. 1992;89:781-784. 14. Hensman C, Newman EL, Shimi SM, et al. Cytotoxicity of electrosurgical smoke produced in an anoxic environment. Am J Surg. 1998;175:240-241. 15. Tomita Y, Mihashi S, Nagata K, et al. Mutagenicity of smoke condensates induced by CO2-laser irradiation and electrocauterization. Mutat Res. 1981;89:145-149. 16. Gloster H, Roenigk R. Risk of acquiring human papillomavirus from the plume produced by the carbon dioxide laser in the treatment of warts. J Am Acad Dermatol. 1995;32:436-441.

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17. Hallmo P, Naess O. Laryngeal papillomatosis with human papillomavirus DNA contracted by a laser surgeon. Eur Arch Otohinolaryngol. 1991;248:425-427. 18. American Occupational Safety and Health Administration. Control of Smoke From Laser/Electric Surgical Procedures. Washington: National Institute for Occupational Safety and Health; 1996:96-128. 19. Lewin JM, Brauer JA, Ostad A. Surgical smoke and the dermatologist. J Am Acad Dermatol. 2011;65:636-641. 20. Edwards BE, Reiman RE. Results of a survey on current surgical smoke control practices. AORN J. 2008;87:739-749.

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